Sting levels as a biomarker for cancer immunotherapy

Abstract

Provided herein are STING and SPARCS genes as biomarkers for determining an effective therapy for treating cancer. Further provided are methods for treating cancer using said biomarkers.

What is claimed is: 
     
         1 . A method for determining a treatment for cancer comprising:
 (i) obtaining a biological sample obtained from a subject having cancer;   (ii) determining the level of Stimulator of IFN Genes (STING); and   (iii) selecting a therapy based on the level of STING.   
     
     
         2 . A method for treating cancer comprising:
 (i) obtaining a biological sample obtained from a subject having cancer;   (ii) determining the level of Stimulator of IFN Genes (STING);   (iii) selecting a therapy based on the level of STING; and   (iv) administering the therapy to the subject.   
     
     
         3 . The method of  claim 1  or  2 , wherein the biological sample is a biopsy sample. 
     
     
         4 . The method of any of  claims 1 - 3 , wherein the level of STING is the level of STING mRNA. 
     
     
         5 . The method of any of  claims 1 - 3 , wherein the level of STING is the level of STING protein. 
     
     
         6 . The method of any of the preceding claims, wherein the cancer is breast cancer, lung cancer, or kidney cancer. 
     
     
         7 . The method of any of the preceding claims, wherein the therapy is selected from at least one of:
 (i) a STING agonist;   (ii) an Immune Checkpoint Blockade (ICB) agent; and   (iii) an interferon gamma signaling agonist;   
       if the level of STING is above a reference value. 
     
     
         8 . The method of  claim 7 , wherein the therapy comprises a STING agonist and an Immune Checkpoint Blockade (ICB) agent. 
     
     
         9 . The method of  claim 7 , wherein the therapy comprises a STING agonist and an interferon gamma signaling agonist. 
     
     
         10 . The method of any of  claims 1 - 6 , wherein the therapy is selected from at least one of a DNA methyltransferase inhibitor and an EZH2 inhibitor if the level of STING is below a reference value. 
     
     
         11 . The method of  claim 10 , wherein the therapy further comprises at least one of:
 (i) a STING agonist;   (ii) an Immune Checkpoint Blockade (ICB) agent; and   (iii) an interferon gamma signaling agonist.   
     
     
         12 . The method of any of  claims 7 - 11 , wherein the STING agonist is selected from SB 11285, MK-1454, or ADU-S100. 
     
     
         13 . The method of any of  claims 7 - 12 , wherein the Immune Checkpoint Blockade (ICB) agent is selected from anti-PD1, anti-PD-L1, or anti-CTLA-4. 
     
     
         14 . The method of any of  claims 7 - 13 , wherein the interferon gamma signaling agonist is selected from poly I:C or PTPN2 inhibitors. 
     
     
         15 . The method of any of  claims 7 - 14 , wherein the DNA methyltransferase inhibitor or EZH2 inhibitor is GSK126, azacitidine, or decitabine. 
     
     
         16 . The method of any of  claims 7 - 15 , wherein the reference is 50% or more above the control level. 
     
     
         17 . The method of  claim 16 , wherein the control level is the level of STING in the same tissue type as the biological sample from a normal healthy subject. 
     
     
         18 . A method of treating a subject having KRAS lung cancer comprising:
 obtaining a biopsy sample from the subject;   determining if the sample has KRAS;LKB1+ or KRAS;LKB1 mutant cancer cells;   administering a STING agonist if the cancer cells are KRAS;LKB1+ cancer cells; and   administering a STING agonist and at least one of a DNA methyltransferase inhibitor and an EZH2 inhibitor if the cancer cells are LKB1 mutant cancer cells.   
     
     
         19 . The method of  claim 18 , further comprising administering one or both of:
 (i) an Immune Checkpoint Blockade (ICB) agent; and   (ii) an interferon gamma signaling agonist.   
     
     
         20 . The method of  claim 18  or  19 , wherein the STING agonist is selected from SB 11285, MK-1454, or ADU-S100. 
     
     
         21 . The method of any of  claims 18 - 20 , wherein the Immune Checkpoint Blockade (ICB) agent is selected from anti-PD1, anti-PD-L1, or anti-CTLA-4. 
     
     
         22 . The method of any of  claims 18 - 21 , wherein the interferon gamma signaling agonist is selected from poly I:C or PTPN2 inhibitors. 
     
     
         23 . The method of any of  claims 18 - 22 , wherein the DNA methyltransferase inhibitor or EZH2 inhibitor is GSK126, azacitidine, or decitabine. 
     
     
         24 . A method of treating a subject having breast cancer comprising:
 obtaining a biopsy sample from the subject comprising breast cancer cells;   determining if the breast cancer cells in the sample are triple negative, HER2+, or luminal B breast cancer cells;   administering a STING agonist if the breast cancer cells are triple negative, HER2+, or luminal B breast cancer cells; and   administering a STING agonist and at least one of a DNA methyltransferase inhibitor and an EZH2 inhibitor if the breast cancer cells are not triple negative, HER2+, or luminal B breast cancer cells.   
     
     
         25 . The method of  claim 24 , further comprising administering one or both of:
 (i) an Immune Checkpoint Blockade (ICB) agent; and   (ii) an interferon gamma signaling agonist.   
     
     
         26 . The method of  claim 24  or  25 , wherein the STING agonist is selected from SB 11285, MK-1454, or ADU-S100. 
     
     
         27 . The method of any of  claims 24 - 26 , wherein the Immune Checkpoint Blockade (ICB) agent is selected from anti-PD1, anti-PD-L1, or anti-CTLA-4. 
     
     
         28 . The method of any of  claims 24 - 27 , wherein the interferon gamma signaling agonist is selected from poly I:C or PTPN2 inhibitors. 
     
     
         29 . The method of any of  claims 24 - 28 , wherein the DNA methyltransferase inhibitor or EZH2 inhibitor is GSK126, azacitidine, or decitabine. 
     
     
         30 . A method for determining a treatment for cancer comprising:
 (i) obtaining a biological sample obtained from a subject having cancer;   (ii) determining the level of one or more SPARCS genes; and   (iii) selecting a therapy based on the level of the one or more SPARCS genes.   
     
     
         31 . A method for treating cancer comprising:
 (i) obtaining a biological sample obtained from a subject having cancer;   (ii) determining the level of one or more SPARCS genes;   (iii) selecting a therapy based on the level of the one or more SPARCS genes; and   (iv) administering the therapy to the subject.   
     
     
         32 . The method of  claim 30  or  31 , wherein the biological sample is a biopsy sample. 
     
     
         33 . The method of any of  claims 30 - 32  wherein the one or more SPARCS genes are selected from TRIM22, TRIM38, IL32, SPATS2L, EPHA3, HERC3, ADAM19, SERPINB9, IFI44L, F3, BEND6, AIG1, MSRB2, TNFRSF9, and ANTXR1. 
     
     
         34 . The method of any of  claims 30 - 33 , wherein the level of the one or more SPARCS genes is the level of mRNA. 
     
     
         35 . The method of any of  claims 30 - 34 , wherein the level of the one or more SPARCS genes is the level of protein. 
     
     
         36 . The method of any of  claims 30 - 35 , wherein the cancer is breast cancer, lung cancer, or kidney cancer. 
     
     
         37 . The method of any of  claims 30 - 36 , wherein the therapy is selected from at least one of:
 (i) a STING agonist;   (ii) an Immune Checkpoint Blockade (ICB) agent; and   (iii) an interferon gamma signaling agonist;   
       if the level of the one or more SPARCS genes is above a reference value. 
     
     
         38 . The method of  claim 37 , wherein the therapy comprises a STING agonist and an Immune Checkpoint Blockade (ICB) agent. 
     
     
         39 . The method of  claim 37 , wherein the therapy comprises a STING agonist and an interferon gamma signaling agonist. 
     
     
         40 . The method of any of  claims 30 - 36 , wherein the therapy is selected from at least one of a DNA methyltransferase inhibitor and an EZH2 inhibitor if the level of the one or more SPARCS genes is below a reference value. 
     
     
         41 . The method of  claim 40 , wherein the therapy further comprises at least one of:
 (i) a STING agonist;   (ii) an Immune Checkpoint Blockade (ICB) agent; and   (iii) an interferon gamma signaling agonist.   
     
     
         42 . The method of any of  claims 37 - 41 , wherein the STING agonist is selected from SB 11285, MK-1454, or ADU-S100. 
     
     
         43 . The method of any of  claims 37 - 42 , wherein the Immune Checkpoint Blockade (ICB) agent is selected from anti-PD1, anti-PD-L1, or anti-CTLA-4. 
     
     
         44 . The method of any of  claims 37 - 43 , wherein the interferon gamma signaling agonist is selected from poly I:C or PTPN2 inhibitors. 
     
     
         45 . The method of any of  claims 37 - 44 , wherein the DNA methyltransferase inhibitor or EZH2 inhibitor is GSK126, azacitidine, or decitabine. 
     
     
         46 . The method of any of  claims 37 - 45 , wherein the reference is 50% or more above the control level. 
     
     
         47 . The method of  claim 46 , wherein the control level is the level of the one or more SPARCS genes in the same tissue type as the biological sample from a normal healthy subject.